Patients with spinal cord injury frequently suffer from respiratory complications due to their inability to cough and clear secretions. In recent animal studies, we have demonstrated that lower thoracic spinal cord stimulation (SCS) results in the generation of large increases in airway pressure and high peak flow rates. This technique, therefore, has the potential to produce an effective cough mechanism in spinal cord injured patients. Prior to clinical trials, however, there are important aspects of this technique that require further characterization. The following objectives are designed to assess the biology of this technique by examining the efficacy of SCS, identifying the specific muscles activated, evaluating the mechanism of their activation, and determining if SCS can prevent the development of expiratory muscle atrophy. In Objective I, the efficacy of SCS in terms of pressure generation will be e valuated by comparing this technique with other methods of expiratory muscle activation. First, SCS will be compared to a less invasive method of activating the expiratory muscles, i.e. surface stimulation of the abdominal wall. Second, we will test our hypothesis that SCS results in near maximal expiratory muscle activation by comparing SCS with direct stimulation of th ventral roots innervating the expiratory muscles. In Objective II, we plan to assess the pattern of muscle recruitment during SCS. Electromyographic techniques will be employed to evaluate the degree of electrical activation of various respiratory muscles located over a broad area of the chest wall. In addition, ablation techniques will be used to quantitate the mechanical contribution of these muscle groups to pressure generation. This data will allow us to assess the functional contribution of different muscle groups during lower thoracic SCS. In Objective III, the mechanism by which the motor nerves innervating the expiratory muscles are activated by lower thoracic SCS will be determined. We plan to assess the pathway(s) by which the ventral roots are stimulated and determine if synapses within the spina cord are involved. In separate trials, the electric field generated by current applied at over the lower thoracic cord will be determined. It is anticipated that this data may provide information leading to further refinement of this technique. In Objective IV, we will characterize the changes in expiratory muscle structure and function, following upper motoneuron denervation. An effective cough is dependent upon optimal function of the expiratory muscles and these muscles are most likely atrophied in patients with spinal cord injury. Therefore, we will also assess the capacity of electrical stimulation to maintain expiratory muscle function in a chronic animal model of spinal cord injury. The results of these studies should resolve important basic science issues concerning this technique in animals, and provide the framework for human clinical trials. Restoration of an effective cough mechanism may allow patients with spinal cord injury to clear secretions more easily, reduce the incidence of respiratory complications such as atelectasis and pneumonia and, ultimately, improve their life quality.